title: Memantine, a promising drug for the prevention of neuropathic pain in rat.
abstract: N-methyl-D-aspartate (NMDA) receptor antagonists are used for post-surgery neuropathic pain but severe side-effects limit their clinical use. Memantine, when given after surgery, shows conflicting results as regard to neuropathic pain alleviation. Here memantine is administered in animals before or after spinal nerve ligation (SNL) in order to evaluate the induced antinociceptive/cognitive effects and associated molecular events, including the phosphorylation of several tyrosine (pTyr(1336), pTyr(1472)) and serine (pSer(1303)) residues in the NR2B subunit of the NMDA receptor. Spinal nerve ligated and sham animals received memantine (20mg/kg/day) or vehicle (1ml/kg/day) by intraperitoneal route. Pre-emptive protocol started 4 days before surgery and continued for 2 days post-surgery. In the post-operative protocol, the 7 day-treatment began on the day of surgery. Tests were done before and after surgery. Tactile allodynia, mechanical hyperalgesia and spatial memory were evaluated by von Frey, Randall & Selitto and Y-maze-tests respectively, and molecular events by western-blot analysis. Spinal nerve ligated animals displayed nociception, impaired memory and increased expression of the 3 phosphorylated residues. Post-operative memantine had no beneficial effect. Pre-emptive memantine prevented the development of post-surgical nociception, impairment of spatial memory and did not increase the expression of pTyr(1472)NR2B at spinal, insular and hippocampal levels. Memantine administered a few days before surgery is a promising strategy to alleviate neuropathic pain development and impairment of cognitive function in animals. The pivotal role of pTyr(1472)NR2B must be studied further, and these findings will now be challenged in patients for the prevention of postsurgical neuropathic pain.
authors.affiliation: Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Laboratoire de Pharmacologie, Facultés de Médecine/Pharmacie, F-63000 Clermont-Ferrand, France; Inserm, U1107 Neuro-Dol, F-63001 Clermont-Ferrand, France; CHU Clermont-Ferrand, Inserm CIC 501, Centre de Pharmacologie Clinique, F-63003 Clermont-Ferrand, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Morel
authors.forename: Monique
authors.initials: M
authors.lastname: Etienne
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Wattiez
authors.forename: Amandine
authors.initials: A
authors.lastname: Dupuis
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Privat
authors.forename: Maryse
authors.initials: M
authors.lastname: Chalus
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.forename: Laurence
authors.initials: L
authors.lastname: Daulhac
authors.forename: Gisèle
authors.initials: G
authors.lastname: Pickering
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control; D008026:Ligation / Q000009:adverse effects; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013127:Spinal Nerves / Q000601:surgery
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine
keywords: Memantine; N-methyl-d-aspartate receptor; NR2B subunit; Neuropathic pain; Spinal nerve ligation; Synaptic plasticity